P1061: CLINICAL FEATURES OF PHILADELPHIA-NEGATIVE MPN DEVELOPED IN ADOLESCENTS AND YOUNG ADULTS IN JAPAN
Authors: Yuka Sugimoto, Eiko Ohya, Keiki Nagaharu, Makoto Ikejiri, Kazuko Ino, Kana Miyazaki, Takeshi Matsumoto, Kohshi Ohishi, Isao Tawara
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: The adolescents and young adults (AYA) population is defined as individuals between 15 and 39 years of age, and accounts for 10-20% of Philadelphia-negative (Ph-) myeloproliferative neoplasm (MPN) diagnoses with an incidence rate of 0.7/100,000 person-years. Little is known about the clinical characteristics of AYA Ph- MPN in Japan and Asia. Aims: We planned a retrospective study for Ph-MPN diagnosed in AYA to elucidate the clinical features of AYA Ph- MPN in Japan. Methods: We retrospectively analyzed 266 patients with MPN diagnosed consecutively from 2008 to 2022 in Mie University and compared the clinical characteristics of 63 AYA Ph- MPN patients to those of 203 non-AYA Ph- MPN. Results: AYA MPN patients accounted for 23.7% of all MPN. The median of the age when abnormal results were found was 33 years (range 16-39), and half of them were diagnosed from abnormal results of an annual health check. 47.6% of them had JAK2 mutation, 25.4% of them were CALR mutated, and only one AYA MPN harbored MPL mutation (1.6%). Compared to non-AYA MPN, AYA patients had higher proportion of essential thrombocythemia (ET) (73.0% vs. 54.1%, p=0.009), higher proportion of triple negative (TN) MPN (20.6% vs. 5.9%, p=0.002), fewer thrombotic events (0% vs. 23.2%, p<0.001) and more vasomotor symptoms before or at diagnosis (4.8% vs.0.5%, p=0.04). As for thrombosis after diagnosis in Japanese AYA MPN, there were fewer venous thrombotic events than arterial thrombotic events (3 vs. 6), which was inconsistent with results in Western countries. AYA MPN did not experience leukemic transformation. In patients with ET, compared to non-AYA ET, Female preponderance (69.6% vs. 49.1%, p=0.02), higher triple negative ET proportion (27.9% vs. 10.3%, p=0.01), and fewer thrombotic events before or at diagnosis (0% vs. 20%, p<0.001) were observed in AYA ET. 26.1% of AYA ET received cytoreductive therapy (CRT). The common reasons for CRT were extreme thrombocythemia (n=3) and acquired von Willebrand disease (vWD) (n=2), that is, prevention for bleeding events. Overall survival (OS) tended to be superior in the AYA ET cohort compared to the non-AYA cohort (median OS: not reached vs. 22.6 years, p=0.096). Myelofibrosis-free survival (MFS) of AYA ET was superior to that of non-AYA ET (median MFS 27.8 years vs. 17.1 years, p=0.003). In AYA polycythemia vera (PV), to a greater or lesser extent, splenomegaly was detected in all patients. Before or at diagnosis, they experienced no thrombotic events. Higher frequency of myelofibrotic transformation was observed in AYA PV compared to non-AYA PV (21.4% vs. 4.3%, p=0.05), which may be due to the longer follow-up duration (2,204 days vs. 782 days, p=0.048). As many as 46.2% of AYA-PV patients received CRT. Splenomegaly (n=2) and bleeding tendency (n=2) were the most common reasons for CRT. OS was not different between AYA and non-AYA in PV (median OS: 15.9 years vs. not reached, p=0.23). However, the difference of MFS was marginally significant between AYA PV and non-AYA PV (median MFS: 12.4 years vs. 15.7 years, p=0.06). In terms of AYA MF, we have only four prefibrotic MF patients. They did not have any thrombosis, bleeding, or disease progression. For the treatments, three of the four patients received CRT. One patient received low-dose aspirin only. Summary/Conclusion: Japanese AYA MPN had less thrombotic events before or at diagnosis, and lower proportion of venous thrombotic events compared to Western AYA MPN patients. It might be due to early detection of MPN by the Japanese health insurance system, which covers annual health check, or different racial characteristics. 33% of AYA MPN needed CRT for the reasons other than the prevention of thrombosis. A larger Japanese cohort is required to elucidate full details of characteristics of Japanese AYA MPN.Keywords: Adult, Adolescents, Thromboembolic events, Myeloproliferative disorder